Retroviruses induce a variety of tumors in vertebrates. A host origin for retroviral oncogenes is implied by the discovery that vertebrate DNA contains highly conserved genes (denoted "c-oncs") that are homologous to retroviral oncogenes. Recent experiments suggest that induction of increased transcription from one of th c-oncs, c-myc, directly causes lymphomas in chickens. The similarity between viral oncogenes and c-onc genes implies a normal role for c-onc proteins in growth cotnrol and/or differentiation. The long-term aim of my research is to elucidate the presumptive roles of c-oncs as cancer genes and as regulators of normal cell growth. Specifically, I will 1) analyze cloned chicken c-myc DNA to determine which regions of c-myc give rise to mRNA and characterize the maturation of c-myc mRNA from larger precursors to determine whether c-myc expression may be controlled at the level of splicing. 2) Determine the sequence of about 2000 bases in c-myc and thus deduce the amino acid sequene of the hitherto unidentified c-myc protein. 3) Investigate a possible role for a c-onc gene in development. Chicken thymus apparently contains a cell fraction enriched for the expression of c-myb, one of the c-onc genes. I will determine whether the expression of c-myb, a putative regulatory gene, fluctuates in parallel with stages in development and/or differentiation in the thymus; such findings would imply a role for c-myb during thymus development. Using cloned c-myb DNAs from mouse and chickens, first I will measure c-myb RNA from organs of various vertebrate species to determine whether elevated levels of c-myb RNA are a general feature of vertebrate thymus. If so, this observation would indicate that c-myb expression is indeed important in thymus physiology. Next, I will fractionate mouse (rather than chicken) thymus into cellular components to determine whether c-myb RNA is expressed primarily within epithelial cells, immature t cells, or immunocompetent T cells. I will follow variations in the expression of c-myb in different fractions of thymus cells during various stages in thymus development. I will monitor specific fluctuations in c-myo expression as a means of assessing the response of cultured thymus cells to the addition of putative mediators of T cell differentiation and thymic involution. If these studies do not prove to be feasible using mice, instead I will investigate c-myo expression in chicken thymus.